Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea.
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Korean J Gastroenterol. 2022 Apr 25;79(4):161-169. doi: 10.4166/kjg.2022.003.
BACKGROUND/AIMS: Previous studies have reported the protective effects of tauroursodeoxycholic acid (TUDCA) on gastric epithelial cells in some animal models, but the precise mechanisms are unclear. This study examined the effects of TUDCA on NF-κB signaling in gastric epithelial cells. Moreover, the protective effects of TUDCA in experimental gastritis models induced by ethanol and NSAID were evaluated and compared with ursodeoxycholic acid (UDCA).
After a pretreatment with TUDCA or UDCA, human gastric epithelial MKN-45 cells were stimulated with tumor necrosis factor (TNF)-α to activate NF-κB signaling. A real-time PCR (RT-PCR) for human interleukin (IL)-1 mRNA was performed. An electrophoretic mobility shift assay (EMSA) and immunoblot analyses were carried out. In murine models, after a pretreatment with TUDCA or UDCA, ethanol and indomethacin were administered via oral gavage. Macroscopic and microscopic assessments were performed to evaluate the preventive effects of TUDCA and UDCA on murine gastritis.
A pretreatment with TUDCA downregulated the IL-1α mRNA levels in MKN-45 cells stimulated with TNF-α, as assessed by RT-PCR. As determined using EMSA, a pretreatment with TUDCA reduced the TNF-α-induced NF-κB DNA binding activity. A pretreatment with TUDCA inhibited IκBα phosphorylation induced by TNF-α, as assessed by immunoblot analysis. TUDCA attenuated the ethanol-induced and NSAID-induced gastritis in murine models, as determined macroscopically and microscopically.
TUDCA inhibited NF-κB signaling in gastric epithelial cells and ameliorated ethanol- and NSAID-induced gastritis in murine models. These results support the potential of TUDCA for the prevention of gastritis in humans.
背景/目的：先前的研究已经报道了牛磺熊去氧胆酸（TUDCA）在某些动物模型中对胃上皮细胞的保护作用，但确切的机制尚不清楚。本研究旨在探讨 TUDCA 对胃上皮细胞 NF-κB 信号通路的影响。此外，还评估并比较了 TUDCA 和熊去氧胆酸（UDCA）在乙醇和非甾体抗炎药诱导的实验性胃炎模型中的保护作用。
用 TUDCA 或 UDCA 预处理人胃上皮细胞 MKN-45 后，用肿瘤坏死因子（TNF）-α刺激以激活 NF-κB 信号通路。采用实时聚合酶链反应（RT-PCR）检测人白细胞介素（IL）-1 mRNA 的表达。进行电泳迁移率变动分析（EMSA）和免疫印迹分析。在小鼠模型中，用 TUDCA 或 UDCA 预处理后，通过口服灌胃给予乙醇和吲哚美辛。通过宏观和微观评估来评估 TUDCA 和 UDCA 对小鼠胃炎的预防作用。
RT-PCR 结果显示，TUDCA 预处理可下调 TNF-α刺激的 MKN-45 细胞中 IL-1α mRNA 的水平。EMSA 结果表明，TUDCA 预处理可降低 TNF-α诱导的 NF-κB DNA 结合活性。免疫印迹分析结果表明，TUDCA 预处理可抑制 TNF-α诱导的 IκBα磷酸化。宏观和微观评估结果表明，TUDCA 可减轻乙醇和非甾体抗炎药诱导的小鼠胃炎。
TUDCA 可抑制胃上皮细胞中的 NF-κB 信号通路，并改善乙醇和非甾体抗炎药诱导的小鼠胃炎。这些结果支持 TUDCA 预防人类胃炎的潜力。
